Vascular, Cardiovascular, and Neurological Actions of Parathyroid-Related Protein

This chapter focuses on the physiology of PTHrP in vascular smooth muscle. It begins with a brief review of its physiological effects in other smooth muscle-containing tissues. In all smooth muscle cell beds studied to date, induction of PTHrP expression occurs in close association with normal physiological stimuli. In each of these smooth muscle beds, application of PTHrP to precontracted smooth muscle preparations induces relaxant activity, precisely mimicking the actions for PTH. Therefore PTHrP represents the physiologically important regulator of smooth muscle tone. PTHrP is expressed in blood vessels in essentially all vascular beds from a broad range of species, including rodent and human fetal blood vessels, adult rat aorta, vena cava, kidney afferent arterioles, artery, and microvasculature, the arterial and venous supply of the mammary gland, the serosal arterioles in avian egg shell gland, and blood vessels of the rat penis. The protein is expressed predominantly in the smooth muscle layer of the vessel, although its expression has also been reported in cultured endothelial cells. The regulation of PTHrP mRNA expression is studied by using cultured vascular smooth muscle cells. In addition to its effects on vascular tone, PTHrP also modulates vascular smooth muscle cell proliferation. The ability of PTHrP to modulate vascular smooth muscle cell growth suggests that the protein might function during the development of the cardiovascular system. Finally, PTHrP plays a significant role in neurological actions.